Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users

RATIONALE: Oral tobacco–derived nicotine products include on!® nicotine pouches (NPs) which are tobacco-leaf free and available in multiple flavors and nicotine levels. Switching completely to NPs from cigarettes and moist smokeless tobacco (MST) has the potential to reduce harm for adult tobacco consumers. However, the dependence potential of NPs is not established. Therefore, we characterized the abuse potential of NPs with different nicotine levels compared to cigarettes and MST. OBJECTIVES: To evaluate nicotine pharmacokinetics (PK) and subjective effects of NPs (ranging from 1.5 to 8 mg nicotine) compared to own brand cigarettes (OBCs) and MST (OBMST). METHODS: We used a randomized, in-clinic, partial single-blind, 7-way crossover design to assess nicotine PK and subjective effects in dual users of cigarettes and MST. RESULTS: The mean nicotine C(max) for NPs increased with nicotine level, ranging from 3.5 ng/mL (1.5 mg NP) to 15.4 ng/mL (8 mg NP), compared with 12.2 ng/mL for OBCs and 9.8 ng/mL for OBMST. Nicotine t(max) was much longer for all NPs and OBMST (32.5–34.4 min) compared to OBCs (8.5 min). Reductions in urges to smoke after use of the 2 mg, 3.5 mg, and 8 mg NPs were not statistically different (p > 0.05) relative to OBC. Also, NPs resulted in lower ratings of positive subjective effects relative to OBCs and OBMST. CONCLUSIONS: Overall, based on the study results and literature reported nicotine PK values for cigarettes and MST, the abuse potential of NPs is not likely to be higher than OBCs and OBMST. NPs may be potentially acceptable switching products for users of cigarettes and MST products. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00213-022-06172-y.